Mercury concentrations in bald eagles across an impacted watershed in Maine, USA.

Mercury (Hg) exposure was evaluated in bald eagles (Haliaeetus leucocephalus) in the lower Penobscot River watershed (PRW) in Maine to assess whether Hg discharges from a chlor-alkali plant (HoltraChem) influenced Hg concentrations in nestling tissues. Mean Hg concentrations in nestling blood and breast feathers sampled in marine and estuarine areas potentially contaminated with Hg from HoltraChem (the potential Hg impact zone) were significantly greater than those from reference sites spanning the Maine coast. To place Hg exposure in the potential Hg impact zone into a broader context, Hg exposure in bald eagle nestlings from four habitat types in the PRW was assessed. Mercury concentrations varied significantly across habitat types within the PRW, generally following the pattern: marine=estuarine

Reversible Oligonucleotide Chain Blocking Enables Bead Capture and Amplification of T-Cell Receptor α and ß Chain mRNAs.

Next-generation sequencing (NGS) has proven to be an exceptionally powerful tool for studying genetic variation and differences in gene expression profiles between cell populations. However, these population-wide studies are limited by their inability to detect variation between individual cells within a population, inspiring the development of single-cell techniques such as Drop-seq, which add a unique barcode to the mRNA from each cell prior to sequencing. Current Drop-seq technology enables capture, amplification, and barcoding of the entire mRNA transcriptome of individual cells. NGS can then be used to sequence the 3'-end of each message to build a cell-specific transcriptional landscape. However, current technology does not allow high-throughput capture of information distant from the mRNA poly-A tail. Thus, gene profiling would have much greater utility if beads could be generated having multiple transcript-specific capture sequences. Here we report the use of a reversible chain blocking group to enable synthesis of DNA barcoded beads having capture sequences for the constant domains of the T-cell receptor α and ß chain mRNAs. We demonstrate that these beads can be used to capture and pair TCRα and TCRß sequences from total T-cell RNA, enabling reverse transcription and PCR amplification of these sequences. This is the first example of capture beads having more than one capture sequence, and we envision that this technology will be of high utility for applications such as pairing the antigen receptor chains that give rise to autoimmune diseases or measuring the ratios of mRNA splice variants in cancer stem cells.

Dose specification and quality assurance of radiation therapy oncology group protocol 95-17; a cooperative group study of iridium-192 breast implants as sole therapy.

PURPOSE: The Radiation Therapy Oncology Group (RTOG) protocol 95-17 was a Phase I/II trial to evaluate multicatheter brachytherapy as the sole method of adjuvant breast radiotherapy for Stage I/II breast carcinoma after breast-conserving surgery. Low- or high-dose-rate sources were allowed. Dose prescription and treatment evaluation were based on recommendations in the International Commission on Radiation Units and Measurements (ICRU), Report 58 and included the parameters mean central dose (MCD), average peripheral dose, dose homogeneity index (DHI), and the dimensions of the low- and high-dose regions. METHODS AND MATERIALS: Three levels of quality assurance were implemented: (1) credentialing of institutions was required before entering patients into the study; (2) rapid review of each treatment plan was conducted before treatment; and (3) retrospective review was performed by the Radiological Physics Center in conjunction with the study chairman and RTOG dosimetry staff. RESULTS: Credentialing focused on the accuracy of dose calculation algorithm and compliance with protocol guidelines. Rapid review was designed to identify and correct deviations from the protocol before treatment. The retrospective review involved recalculation of dosimetry parameters and review of dose distributions to evaluate the treatment. Specifying both central and peripheral doses resulted in uniform dose distributions, with a mean dose homogeneity index of 0.83 +/- 0.06. CONCLUSIONS: Vigorous quality assurance resulted in a high-quality study with few deviations; only 4 of 100 patients were judged as representing minor variations from protocol, and no patient was judged as representing major deviation. This study should be considered a model for quality assurance of future trials.

Rigidification of a flexible protease inhibitor variant upon binding to trypsin.

The Tyr35-->Gly replacement in bovine pancreatic trypsin inhibitor (BPTI) has previously been shown to dramatically enhance the flexibility of the trypsin-binding region of the free inhibitor and to destabilize the interaction with the protease by about 3 kcal/mol. The effects of this replacement on the enzyme-inhibitor interaction were further studied here by X-ray crystallography and isothermal titration calorimetry (ITC). The co-crystal structure of Y35G BPTI bound to trypsin was determined using 1.65 A resolution X-ray diffraction data collected from cryopreserved crystals, and a new structure of the complex with wild-type BPTI under the same conditions was determined using 1.62 A data. These structures reveal that, in contrast to the free protein, Y35G BPTI adopts a conformation nearly identical with that of the wild-type protein, with a water-filled cavity in place of the missing Tyr side-chain. The crystallographic temperature factors for the two complexes indicate that the mutant inhibitor is nearly as rigid as the wild-type protein when bound to trypsin. Calorimetric measurements show that the change in enthalpy upon dissociation of the complex is 2.5 kcal/mol less favorable for the complex containing Y35G BPTI than for the complex with the wild-type inhibitor. Thus, the destabilization of the complex resulting from the Y35G replacement is due to a more favorable change in entropy upon dissociation. The heat capacity changes for dissociation of the mutant and wild-type complexes were very similar, suggesting that the entropic effects probably do not arise from solvation effects, but are more likely due to an increase in protein conformational entropy upon dissociation of the mutant inhibitor. These results define the biophysical role of a highly conserved core residue located outside of a protein-binding interface, demonstrating that Tyr35 has little impact on the trypsin-bound BPTI structure and acts primarily to define the structure of the free protein so as to maximize binding affinity.

The US radiation dosimetry standards for 60Co therapy level beams, and the transfer to the AAPM accredited dosimetry calibration laboratories.

This work reports the transfer of the primary standard for air kerma from the National Institute of Standards and Technology (NIST) to the secondary laboratories accredited by the American Association of Physics in Medicine (AAPM). This transfer, performed in August of 2003, was motivated by the recent revision of the NIST air-kerma standards for 60Co gamma-ray beams implemented on July 1, 2003. The revision involved a complete recharacterization of the two NIST therapy-level 60Co gamma-ray beam facilities, resulting in new values for the air-kerma rates disseminated by the NIST. Some of the experimental aspects of the determination of the new air-kerma rates are briefly summarized here; the theoretical aspects have been described in detail by Seltzer and Bergstrom ["Changes in the U.S. primary standards for the air-kerma from gamma-ray beams," J. Res. Natl. Inst. Stand. Technol. 108, 359-381 (2003)]. The standard was transferred to reference-class chambers submitted by each of the AAPM Accredited Dosimetry Calibration Laboratories (ADCLs). These secondary-standard instruments were then used to characterize the 60Co gamma-ray beams at the ADCLs. The values of the response (calibration coefficient) of the ADCL secondary-standard ionization chambers are reported and compared to values obtained prior to the change in the NIST air-kerma standards announced on July 1, 2003. The relative change is about 1.1% for all of these chambers, and this value agrees well with the expected change in chambers calibrated at the NIST or at any secondary-standard laboratory traceable to the new NIST standard.

Identification of a residue critical for maintaining the functional conformation of BPTI.

The effects of amino acid replacements on the backbone dynamics of bovine pancreatic trypsin inhibitor (BPTI) were examined using 15N NMR relaxation experiments. Previous studies have shown that backbone amide groups within the trypsin-binding region of the wild-type protein undergo conformational exchange processes on the micros time scale, and that replacement of Tyr35 with Gly greatly increases the number of backbone atoms involved in such motions. In order to determine whether these mutational effects are specific to the replacement of this residue with Gly, six additional replacements were examined in the present study. In two of these, Tyr35 was replaced with either Ala or Leu, and the other four were single replacements of Tyr23, Phe33, Asn43 or Asn44, all of which are highly buried in the native structure and conserved in homologous proteins. The Y35A and Y35L mutants displayed dynamic properties very similar to those of the Y35G mutant, with the backbone segments including residues 10-19 and 32-44 undergoing motions revealed by enhanced 15N transverse relaxation rates. On the other hand, the Y23L, N43G and N44A substitutions caused almost no detectable changes in backbone dynamics, on either the ns-ps or ms-micros time scales, even though each of these replacements significantly destabilizes the native conformation. Replacement of Phe33 with Leu caused intermediate effects, with several residues that have previously been implicated in motions in the wild-type protein displaying enhanced transverse relaxation rates. These results demonstrate that destabilizing amino acid replacements can be accommodated in a native protein with dramatically different effects on conformational dynamics and that Tyr35 plays a particularly important role in defining the conformation of the trypsin-binding site of BPTI.

TG-51: experience from 150 institutions, common errors, and helpful hints.

The Radiological Physics Center (RPC) is a resource to the medical physics community for assistance regarding dosimetry procedures. Since the publication of the AAPM TG-51 calibration protocol, the RPC has responded to numerous phone calls raising questions and describing areas in the protocol where physicists have had problems. At the beginning of the year 2000, the RPC requested that institutions participating in national clinical trials provide the change in measured beam output resulting from the conversion from the TG-21 protocol to TG-51. So far, the RPC has received the requested data from approximately 150 of the approximately 1300 institutions in the RPC program. The RPC also undertook a comparison of TG-21 and TG-51 and determined the expected change in beam calibration for ion chambers in common use, and for the range of photon and electron beam energies used clinically. Analysis of these data revealed two significant outcomes: (i) a large number (approximately 1/2) of the reported calibration changes for photon and electron beams were outside the RPC's expected values, and (ii) the discrepancies in the reported versus the expected dose changes were as large as 8%. Numerous factors were determined to have contributed to these deviations. The most significant factors involved the use of plane-parallel chambers, the mixing of phantom materials and chambers between the two protocols, and the inconsistent use of depth-dose factors for transfer of dose from the measurement depth to the depth of dose maximum. In response to these observations, the RPC has identified a number of circumstances in which physicists might have difficulty with the protocol, including concerns related to electron calibration at low energies (R50<2 cm), and the use of a cylindrical chamber at 6 MeV electrons. In addition, helpful quantitative hints are presented, including the effect of the prescribed lead filter for photon energy measurements, the impact of shifting the chamber depth for photon depth-dose measurements, and the impact of updated stopping-power data used in TG-51 versus that used in TG-21, particularly for electron calibrations.

Predictability of electron cone ratios with respect to linac make and model.

In the past, the Radiological Physics Center (RPC) has developed standard sets of photon depth-dose and wedge-factor data, specific to the make, model, and wedge design of the linear accelerator (linac). In this paper, the RPC extends the same concept to electron-cone ratios. Since 1987, the RPC has measured and documented cone-ratio (CR) values during on-site dosimetry review visits to institutions participating in National Cancer Institute cooperative clinical trials. Data have been collected for approximately 500 electron beams from a wide spectrum of linac models. The analysis presented in this paper indicates that CR values are predictable to 2% to 3% (two standard deviations) for a given make and model of linac with a few exceptions. The analysis also revealed some other interesting systematics. For some models, such as the Varian Clinac 2500 and the Elekta/Philips SL18, SL20, and SL25, CR values were nearly identical for cone sizes 15 cm x 15 cm (or 14 cm x 14 cm) and 20 cm x 20 cm across the range of available energies. Certain models of the same make of linac, such as the Mevatron MD, KD, and 6700 series models or the Clinac 2100 and 2300 models, exhibited indistinguishable CRs. Irrespective of linac model, two consistent general trends were observed: namely, an increase in CR value with incident beam energy for cone sizes smaller than 10 cm x 10 cm and a decrease with energy for cone sizes larger than 10 cm x 10 cm. These data are valuable to the RPC as a quality assurance remote-monitoring tool to identify potential dosimetry errors. The physics community will also find the data useful in several ways: as a redundant check for clinical values in use, to validate the values measured during commissioning of new machines or to ensure consistency of values measured during annual quality assurance procedures.

Calculated absorbed-dose ratios, TG51/TG21, for most widely used cylindrical and parallel-plate ion chambers over a range of photon and electron energies.

Task Group 51 (TG51), of the Radiation Therapy Committee of the American Association of Physicists in Medicine (AAPM), has developed a calibration protocol for high-energy photon and electron therapy beams based on absorbed dose standards. This protocol is intended to replace the air-kerma based protocol developed by an earlier AAPM task group (TG21). Conversion to the newer protocol introduces a change in the determined absorbed dose. In this work, the change in dose is expressed as the ratio of the doses (TG51/TG21) based on the two protocols. Dose is compared at the TG-51 reference depths of 10 cm for photons and d(ref) for electrons. Dose ratios are presented for a variety of ion chambers over a range of photon and electron energies. The TG51/TG21 dose ratios presented here are based on the dosimetry factors provided by the two protocols and the chamber-specific absorbed dose and exposure calibration factors (N60Co(D,w) and Nx) provided by the Accredited Dosimetry Calibration Laboratory (ADCL) at The University of Texas, M. D. Anderson Cancer Center (MDACC). As such, the values presented here represent the expected discrepancies between the two protocols due only to changes in the dosimetry parameters and the differences in chamber-specific dose and air-kerma standards. These values are independent of factors such as measurement uncertainties, setup errors, and inconsistencies arising from the mix of different phantoms and ion chambers for the two protocols. Therefore, these ratios may serve as a guide for institutions performing measurements for the switch from TG21-to-TG51 based calibration. Any significant deviation in the ratio obtained from measurements versus those presented here should prompt a review to identify possible errors and inconsistencies. For all cylindrical chambers included here, the TG51/TG21 dose ratios are the same within +/-0.6%, irrespective of the make and model of the chamber, for each photon and electron beam included. Photon beams show the TG51/TG21 dose ratios decreasing with energy, whereas electrons exhibit the opposite trend. The dose ratio for photons is near 1.00 at 18 mV increasing to near 1.01 at 4 mV while the dose ratio for electrons is near 1.02 at 20 MeV decreasing only 0.5% to near 1.015 at 6 MeV. For parallel-plate chambers, the situation is complicated by the two possible methods of obtaining calibration factors: through an ADCL or through a cross-comparison with a cylindrical chamber in a high-energy electron beam. For some chambers, the two methods lead to significantly different calibration factors, which in turn lead to significantly different TG51/TG21 results for the same chamber. Data show that if both N60Co(D,w) and Nx are obtained from the same source, namely an ADCL or a cross comparison, the TG51/TG21 results for parallel-plate chambers are similar to those for cylindrical chambers. However, an inconsistent set of calibration factors, i.e., using N60Co(D,w) x k(ecal) from an ADCL but Ngas from a cross comparison or vice versa, can introduce an additional uncertainty up to 2.5% in the TG51/TG21 dose ratios.

Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years COMS report no. 16.

OBJECTIVE: To report visual acuity during the first three years after iodine 125 (I(125)) brachytherapy for medium-sized choroidal melanoma and to identify important baseline and treatment factors associated with posttreatment visual acuity in a group of patients who were treated and observed prospectively as part of a large, randomized clinical trial. DESIGN: Observational case series within a randomized, multicenter study. PARTICIPANTS: Patients enrolled in the Collaborative Ocular Melanoma Study randomized trial of I(125) brachytherapy versus enucleation had choroidal melanoma of at least 2.5 mm but no more than 10.0 mm in apical height, and no more than 16.0 mm in largest basal dimension. One thousand three hundred seventeen patients enrolled from February 1987 through July 1998; 657 patients were assigned to I(125) brachytherapy. Visual acuity data for 623 patients who received I(125) brachytherapy as randomly assigned and who have been observed for at least 1 year were analyzed for this report. METHODS: Under study protocol, an ophthalmic evaluation, including best-corrected visual acuity measurement of each eye, was performed at baseline, every 6 months thereafter for 5 years, and once yearly thereafter. Two poor vision outcomes, visual acuity of 20/200 or worse that was confirmed at the next follow-up examination and loss of six lines or more of visual acuity from baseline that was confirmed at the next follow-up examination, were analyzed to identify baseline and treatment characteristics that were associated with posttreatment visual acuity. RESULTS: At baseline, median visual acuity in the eye with choroidal melanoma was 20/32, with 70% of eyes having 20/40 or better and 10% of eyes having 20/200 or worse visual acuity. Three years after I(125) brachytherapy, median visual acuity was 20/125, with 34% having 20/40 or better and 45% having 20/200 or worse visual acuity, including eyes that were enucleated within 3 years of treatment. Life-table estimates of percentages of patients who lost six or more lines of visual acuity from baseline, a quadrupling of the minimum angle of resolution, with this finding confirmed at the next 6-month follow-up examination, were 18% by 1 year, 34% by 2 years, and 49% by 3 years after treatment. Life-table estimates of percentages of patients with baseline visual acuity better than 20/200 whose visual acuity decreased to 20/200 or worse, confirmed at the next follow-up examination, were 17% by 1 year, 33% by 2 years, and 43% by 3 years after treatment. As soon as a poor vision outcome was observed, improvement of visual acuity to a level that no longer met the definition for a poor vision outcome was rare. Greater baseline tumor apical height and shorter distance between the tumor and the foveal avascular zone (FAZ) were the factors most strongly associated with loss of six or more lines of visual acuity after treatment. These two factors and baseline visual acuity also were strongly associated with visual acuity 20/200 or worse after treatment. Patient history of diabetes, presence of tumor-associated retinal detachment, and tumors that were not dome shaped also were associated with greater risk for both of the poor vision outcomes. CONCLUSIONS: Forty-three percent to 49% of treated eyes had substantial impairment in visual acuity by 3 years after I(125) brachytherapy, defined as a loss of six or more lines of visual acuity from the pretreatment level (49% of eyes) or visual acuity of 20/200 or worse (43% of eyes) that was confirmed at the next 6-month examination. Patients with a history of diabetes and patients whose eyes had thicker tumors, tumors close to or beneath the FAZ, tumor-associated retinal detachment, or tumors that were not dome shaped were those most likely to have a poor visual acuity outcome within 3 years after I(125) brachytherapy.

Postcardiopulmonary bypass hypoxemia: a prospective study on incidence, risk factors, and clinical significance.

OBJECTIVE: To evaluate the clinical significance of low arterial oxygen tension-inspired oxygen concentration (PaO2-FIO2) ratio, as a measure of hypoxemia, in the early period after cardiac surgery with cardiopulmonary bypass (CPB); and to evaluate the preoperative, intraoperative, and postoperative factors contributing to the development of hypoxemia within the first 24 hours after cardiac surgery with CPB. DESIGN: Prospective observational study. SETTING: University hospital. PARTICIPANTS: Patients who underwent elective or emergency cardiac surgery with CPB (n = 466). INTERVENTIONS: Preoperative clinical and laboratory data were recorded, as were intraoperative and postoperative data regarding the PaO2-FIO2 ratio, fluid and drug therapy, and chest radiograph. Data analysis evaluated hypoxemia as depicted by the PaO2-FIO2 ratios at 1, 6, and 12 hours after surgery. Thereafter, the effect of the PaO2-FIO2 ratios on time to extubation, lung injury, and length of hospital stay was evaluated. The risk factors were analyzed in 3 separate periods: preoperative, intraoperative, and postoperative. Univariate and multivariate analyses were performed on each period separately. All data were analyzed in 2 consecutive steps: univariate analysis and multivariate analysis. MEASUREMENTS AND MAIN RESULTS: PaO2-FIO2 ratios after CPB were significantly lower compared with baseline values. Six patients (1.32%) met the clinical criteria compatible with acute lung injury. All 6 patients had prompt recovery. Significant risk factors for hypoxemia were age, obesity, reduced cardiac function, previous myocardial infarction, emergency surgery, baseline chest radiograph with alveolar edema, high creatinine level, prolonged CPB time, decreased baseline PaO2-FIO2, use of dopamine after discontinuation of CPB, coronary artery bypass grafting, use of left internal mammary artery, higher pump flow requirement during CPB, increased level of hemoglobin or total protein content, persistent hypothermia 2 and 6 hours after surgery, requirement for reexploration, event requiring reintubation, and chest radiograph with alveolar edema 1 hour after surgery. Six hours after surgery, a lower PaO2-FIO2 ratio correlated significantly with time to extubation and lung injury. CONCLUSIONS: This study shows that despite improvements in the technique of CPB, hypoxemia depicted by low PaO2-FIO2 ratios is common in patients after CPB. It is short lived, however, and has minimal effect on the postoperative clinical course of these patients.

Recommendations of the American Association of Physicists in Medicine on 103Pd interstitial source calibration and dosimetry: implications for dose specification and prescription.

The National Institute of Standards and Technology (NIST) introduced a national standard for air kerma strength of the ThreaSeed Model 200 103Pd source (the only 103Pd seed available until 1999) in early 1999. Correct implementation of the NIST-99 standard requires the use of dose rate constants normalized to this same standard. Prior to the availability of this standard, the vendor's calibration procedure consisted of intercomparing Model 200 seeds with a 109Cd source with a NIST-traceable activity calibration. The AAPM undertook a comprehensive review of 103Pd source dosimetry including (i) comparison of the vendor and NIST-99 calibration standards; (ii) comparison of original Task Group 43 dosimetry parameters with more recent studies; (iii) evaluation of the vendor's calibration history; and (iv) evaluation of administered-to-prescribed dose ratios from the introduction of 103Pd sources in 1987 to the present. This review indicates that for a prescribed dose of 115 Gy, the administered doses were (a) 124 Gy for the period 1988-1997 and (b) 135 Gy for the period 1997-1999. The AAPM recommends that the following three steps should be undertaken concurrently to implement correctly the 1999 dosimetry data and NIST-99 standard for 103Pd source: (1) the vendor should provide calibrations in terms of air kerma strength traceable to NIST-99 standard, (2) the medical physicist should update the treatment planning system with properly normalized (to NIST-99) dosimetry parameters for the selected 103Pd source model, and (3) the radiation oncologist in collaboration with the medical physicist should decide which clinical experience they wish to duplicate; the one prior to 1997 or the one from 1997 to 1999. If the intent is to duplicate the experience prior to 1997, which is backed by the long-term follow-up and published outcome studies, then the prior prescriptions of 115 Gy should be replaced by 124 Gy to duplicate that experience.

Pulmonary vascular response of the coati to chronic hypoxia.

The unusually muscular pulmonary arteries normally present in cattle and swine residing at low altitude are associated with a rapid development of severe pulmonary hypertension when those animals are moved to high altitude. Because these species lack collateral ventilation, they appear to have an increased dependence on hypoxic vasoconstriction to maintain normal ventilation-perfusion balance, which, in turn, maintains thickened arterial walls. The only other species known to lack collateral ventilation is the coati, which, similarly, has thick-walled pulmonary arteries. We tested the hypothesis that coatis will develop severe high-altitude pulmonary hypertension by exposing six of these animals (Nasua narica) to a simulated altitude of 4,900 m for 6 wk. After the exposure, pulmonary arterial pressures were hardly elevated, right ventricular hypertrophy was minimal, there was no muscularization of pulmonary arterioles, and, most surprising of all, there was a decrease in medial thickness of muscular pulmonary arteries. These unexpected results break a consistent cross-species pattern in which animals with thick muscular pulmonary arteries at low altitude develop severe pulmonary hypertension at high altitude.

Comparison between TG-51 and TG-21: Calibration of photon and electron beams in water using cylindrical chambers.

A new calibration protocol, developed by the AAPM Task Group 51 (TG-51) to replace the TG-21 protocol, is based on an absorbed-dose to water standard and calibration factor (N(D,w)), while the TG-21 protocol is based on an exposure (or air-kerma) standard and calibration factor (N(x)). Because of differences between these standards and the two protocols, the results of clinical reference dosimetry based on TG-51 may be somewhat different from those based on TG-21. The Radiological Physics Center has conducted a systematic comparison between the two protocols, in which photon and electron beam outputs following both protocols were compared under identical conditions. Cylindrical chambers used in this study were selected from the list given in the TG-51 report, covering the majority of current manufacturers. Measured ratios between absorbed-dose and air-kerma calibration factors, derived from the standards traceable to the NIST, were compared with calculated values using the TG-21 protocol. The comparison suggests that there is roughly a 1% discrepancy between measured and calculated ratios. This discrepancy may provide a reasonable measure of possible changes between the absorbed-dose to water determined by TG-51 and that determined by TG-21 for photon beam calibrations. The typical change in a 6 MV photon beam calibration following the implementation of the TG-51 protocol was about 1%, regardless of the chamber used, and the change was somewhat smaller for an 18 MV photon beam. On the other hand, the results for 9 and 16 MeV electron beams show larger changes up to 2%, perhaps because of the updated electron stopping power data used for the TG-51 protocol, in addition to the inherent 1% discrepancy presented in the calibration factors. The results also indicate that the changes may be dependent on the electron energy.

AAPM's TG-51 protocol for clinical reference dosimetry of high-energy photon and electron beams.

A protocol is prescribed for clinical reference dosimetry of external beam radiation therapy using photon beams with nominal energies between 60Co and 50 MV and electron beams with nominal energies between 4 and 50 MeV. The protocol was written by Task Group 51 (TG-51) of the Radiation Therapy Committee of the American Association of Physicists in Medicine (AAPM) and has been formally approved by the AAPM for clinical use. The protocol uses ion chambers with absorbed-dose-to-water calibration factors, N(60Co)D,w which are traceable to national primary standards, and the equation D(Q)w = MkQN(60Co)D,w where Q is the beam quality of the clinical beam, D(Q)w is the absorbed dose to water at the point of measurement of the ion chamber placed under reference conditions, M is the fully corrected ion chamber reading, and kQ is the quality conversion factor which converts the calibration factor for a 60Co beam to that for a beam of quality Q. Values of kQ are presented as a function of Q for many ion chambers. The value of M is given by M = PionP(TP)PelecPpolMraw, where Mraw is the raw, uncorrected ion chamber reading and Pion corrects for ion recombination, P(TP) for temperature and pressure variations, Pelec for inaccuracy of the electrometer if calibrated separately, and Ppol for chamber polarity effects. Beam quality, Q, is specified (i) for photon beams, by %dd(10)x, the photon component of the percentage depth dose at 10 cm depth for a field size of 10x10 cm2 on the surface of a phantom at an SSD of 100 cm and (ii) for electron beams, by R50, the depth at which the absorbed-dose falls to 50% of the maximum dose in a beam with field size > or =10x10 cm2 on the surface of the phantom (> or =20x20 cm2 for R50>8.5 cm) at an SSD of 100 cm. R50 is determined directly from the measured value of I50, the depth at which the ionization falls to 50% of its maximum value. All clinical reference dosimetry is performed in a water phantom. The reference depth for calibration purposes is 10 cm for photon beams and 0.6R50-0.1 cm for electron beams. For photon beams clinical reference dosimetry is performed in either an SSD or SAD setup with a 10x10 cm2 field size defined on the phantom surface for an SSD setup or at the depth of the detector for an SAD setup. For electron beams clinical reference dosimetry is performed with a field size of > or =10x10 cm2 (> or =20x20 cm2 for R50>8.5 cm) at an SSD between 90 and 110 cm. This protocol represents a major simplification compared to the AAPM's TG-21 protocol in the sense that large tables of stopping-power ratios and mass-energy absorption coefficients are not needed and the user does not need to calculate any theoretical dosimetry factors. Worksheets for various situations are presented along with a list of equipment required.

Determination of the tissue attenuation factor along two major axes of a high dose rate (HDR) 192Ir source.

Quantitative information on photon scattering around brachytherapy sources is needed to develop dose calculation formalisms capable of predicting dosimetric parameters with minimal empiricism. Photon absorption and scatter around brachytherapy sources can be characterized using the tissue attenuation factor, defined as the ratio of dose in water to water kerma in free space. In this study, the tissue attenuation factor along two major axes of a high dose rate (HDR) 192Ir source was determined by TLD measurements and MCNP Monte Carlo calculations. A calculational method is also suggested to derive the tissue attenuation factor along the longitudinal source axis from the factor along the transverse axis, using published anisotropy data as input. TLD and Monte Carlo results agreed with each other for both source axes within the statistical uncertainty (approximately +/- 5%) of Monte Carlo calculations. Comparison with published data, available only for the transverse source axis, also showed good agreement within +/- 5%. The shape and magnitude of the tissue attenuation factor are found to be remarkably different between the two axes. The tissue attenuation factor reaches a maximum value of about 1.4 at 8 cm from the source along the longitudinal source axis, while a maximum value of about 1.04 occurs at 3-4 cm from the source along the transverse axis. The calculated tissue attenuation factor along the longitudinal source axis generally reproduced the TLD and Monte Carlo results within +/- 5% at most radial distances.

Guidance to users of Nycomed Amersham and North American Scientific, Inc., I-125 interstitial sources: dosimetry and calibration changes: recommendations of the American Association of Physicists in Medicine Radiation Therapy Committee Ad Hoc Subcommittee on Low-Energy Seed Dosimetry.

Dose calculations to patients undergoing implantation of 125I interstitial brachytherapy sources are affected by two recent changes in low-energy seed dosimetry: (a) implantation of a new primary air-kerma strength standard at the National Institute of Standards and Technology (NIST) on 1 January 1999 and (b) publication of revised dose-rate distributions in AAPM's Task Group 43 Report. The guidance herein represents AAPM's recommendations for users of 125I interstitial seed products marketed prior to 1 January 1999 (Nycomed Amersham models 6711 and 6702 and North American Scientific, Inc. models 3631 A/S and 3631 A/M. Implementation of Task Group 43 (TG43) 125I dose calculations involves revising data stored in files of radiation treatment planning software and lowering the prescribed dose to be delivered to patients by as much as 15% to avoid modifying the dose actually delivered to patients. The magnitude of the dose prescription change depends on the dosimetry data used prior to TG43 and the implant geometry. Adapting to the revised NIST calibration standard requires the user to increase the dose-rate constant (or its equivalent by 11.5%) but does not require modification of the prescribed dose. Failure to correctly implement these modifications can result in 20% or even 30% errors.

An empirical relationship for determining photon beam quality in TG-21 from a ratio of percent depth doses.

A key component of the Radiological Physics Center's (RPC) on-site dosimetry review visits are photon beam calibrations for which determination of the energy of the x ray is a key element. The ratio of ionizations, TPR20/TPR10, for a 10 cm x 10 cm field at depths of 20 and 10 cm for a constant SCD is used as a quantitative measure of beam quality in the Task Group 21 protocol. The RPC has measured both TPR20/TPR10 and the corresponding ratio of percent depth dose (D20/D10) at a constant SSD for 685 photon beams (4-25 MV) for most makes and models if accelerators. A strong correlation between TPR20/TPR10 and D20/D10 is presented which allows the determination of the TPR ratio from the measurement of the ratio of percent depth doses. An analysis of the uncertainty introduced in the TG-21 factors (L/rho, Pwall, Prepl) caused by the spread in the measured data and translated into the determination of the TPR ratio results in an insignificant error (< 0.3%). This empirical relationship provides an alternate technique for quantifying the beam quality defined in the TG-21 protocol without surrendering any loss of precision in output calibration. This technique may be found by those who calibrate at a fixed SSD to be an easier and quicker method.